The present invention relates to a method for preparing an aqueous emulsion for coating solid pharmaceutical preparations.
Solid pharmaceutical preparations have been coated with a variety of coating bases depending on the applications thereof. In an enteric coated pharmaceutical preparation, the enteric coating serves to not only protect a drug having low resistance to acids from the attack thereof in the stomach, but also protect the gastric mucous membrane from the attack of the drug which may stimulate and damage the wall of the stomach and is dissolved after the arrival at the intestines wherein the pharmaceutical preparation shows its desired pharmacological action. In addition, a sustained release pharmaceutical preparation provided with an insoluble coating ensures the control of the release properties of a drug and continuously shows its pharmacological effect over a long time period. There have been used cellulosic polymers as enteric coating bases. Examples of water-insoluble cellulosic polymers usable as enteric coating bases include cellulose acetate phthalate, hydroxypropylmethyl cellulose phthalate, hydroxypropylmethyl cellulose acetate succinate and carboxymethylethyl cellulose. Moreover, bases for sustained release coating films may, for instance, be ethyl cellulose. These polymers as coating bases are used in the coating treatment of pharmaceutical preparations in the form of a solution in an organic solvent or an aqueous latex or an aqueous dispersion. Recently, however, the use of organic solvents has been regulated from the viewpoint of environmental pollution and accordingly, coating treatments which makes use of aqueous systems have widely been adopted.
There have been known methods for dispersing cellulosic polymers in water, for instance, a method comprising adding the polymers to water together with salts or neutralizing the carboxyl groups of the polymers and a method comprising dispersing, in water, the polymers which are pulverized into fine particles in advance.
With regard to the former method, Japanese Patent Application Publication No. 61-56221 discloses a method which comprises the steps of emulsifying cellulose acetate phthalate, then adding a phosphoric acid salt as an anticoagulant and spray-drying the resulting emulsion to give polymer powder capable of being redispersed in water. In this method, the emulsification of ethyl cellulose and cellulose acetate phthalate is carried out according to the method as disclosed in U.S. Pat. No. 4,177,177. Moreover, Japanese Patent Provisional Publication No. 56-30913 discloses a method in which cellulose acetate phthalate or hydroxypropylmethyl cellulose phthalate is used in coating operations in the form of an aqueous solution neutralized with ammonia. Furthermore, Japanese Patent Provisional Publication No. 58-135807 discloses a method comprising the steps of dissolving a cellulose derivative in water after neutralization with an alkali and then adding a carboxylic acid. In all of the solid pharmaceutical preparations prepared according to these methods, alkali or ammonium salts of carboxylic acids remain in the coated films of the preparations. The alkali and ammonium salts are highly hygroscopic by nature and accordingly, the quality of such solid pharmaceutical preparations is impaired.
In respect of the latter method, Japanese Patent Application Publication No. 56-12614 discloses a method comprising dispersing a cellulosic polymer having an average particle size of not more than 100 .mu.m in water which comprises a gelling agent (a plasticizer) and has a boiling point of not less than 100.degree. C. Moreover, Japanese Patent Application Publication Nos. 57-53329 and 58-55125 disclose the use of triacetin or triethyl citrate as a gelling agent. If a polymer is mechanically pulverized to disperse it in water, the particle size of the resulting polymer particles is more than 1 .mu.m. The use of a plasticizer is indispensable to the dispersion, in water, of polymer particles having a particle size of more than 1 .mu.m and, otherwise, these polymer particles are softened through heating and cause coagulation and precipitation within the resulting dispersions.
Japanese Patent Application Publication No. 3-39490 discloses a method for improving the technique for coating an aqueous cellulose system by reducing the particle size of a cellulosic polymer dispersed in water through emulsification. In this patent, the emulsification is carried out according to the method as disclosed in U.S. Pat. No. 4,177,177. More specifically, a polymer solution is first prepared by dissolving the cellulosic polymer in a water-immiscible organic solvent. Thereafter a hydrocarbon (such as cetyl alcohol) having not less than 8 carbon atoms as a stabilizer and a surfactant are added to the polymer solution and then the resulting polymer solution is treated with a special emulsifying device such as a high-pressure homogenizer to give an emulsion. As has been discussed above in detail, the conventional aqueous coating solutions include components other than the cellulosic polymers, such as stabilizers and surfactants. These components often impair the resistance to acids and stability of the resulting enteric coated pharmaceutical preparations. For this reason, there has been desired for the development of a coating solution having a simple composition as much as possible.